SUMMARY
The research of Hon-Chi Lee, M.D., Ph.D., involves several areas that are related to the regulation of ion channels in the cardiovascular system. Ion channels are critical in managing the traffic of ions across cell membranes. These channels are major determinants of blood vessel relaxation and the formation and propagation of heartbeats. Dr. Lee's study areas include unusual coronary artery behavior in diabetes and irregular heart rhythms such as atrial fibrillation. His research uses cultured cells, isolated tissues, genetically engineered mouse models, human tissue and clinical studies.
Focus areas
- Unusual ionic regulation in diabetic coronary arteries. Dr. Lee studies how diabetes affects irregular blood vessel regulation with specific focus on coronary arteries. The big potassium (BK) channel is a major determinant of coronary arterial tone and blood perfusion of the heart. Using animal models of type 1 and type 2 diabetes, Dr. Lee found that BK channels are damaged in expression, function, and regulation in diabetes. Cellular synthesis, processing and degradation of these channels are unusual in diabetes, and Dr. Lee has identified the molecular mechanisms that underlie this compromised regulation.
- Role of TRPC6 channel in chemotherapy-induced cardiotoxicity. Chemotherapeutic agents such as doxorubicin are frequently used to treat cancer. These agents are known to cause heart failure. Even when dose-limiting guidelines are followed, a subset of people develop heart failure when given these agents. Through genome-wide association studies, TRPC6 has been identified as a vulnerable target for doxorubicin-induced cardiotoxicity. Dr. Lee has delineated the mechanisms involved in mutations or variants in TRPC6 that may lead to heart failure after treatment with doxorubicin.
- Postoperative atrial fibrillation. Atrial fibrillation is a common complication occurring in 30% to 40% of people after heart surgery. The cause of atrial fibrillation after heart surgery is unclear but appears to be different from that of atrial fibrillation in the general population. Dr. Lee reviewed records of all the people who had heart surgery at Mayo Clinic in the last 20 years and tried to identify the factors that may have led to postoperative atrial fibrillation. In addition, Dr. Lee strives to develop a risk score that may help in predicting which individuals are at risk for this condition after heart surgery.
Significance to patient care
In his research, Dr. Lee uses cutting-edge electrophysiological methods to measure ion channel activity and regulation using cells from animal models and specimens from people. His research increases the understanding of the pathophysiological workings of diabetic vascular diseases and also may open doors for new and effective treatments.
Results of his TRPC6 and cardiotoxicity project may be of great value. These studies help find individuals who are likely to develop heart failure when treated with doxorubicin and related medicines. Hence, there could be dose changes or other approaches in the treatment of such people to reduce risk.
Finding the people who are at risk of developing postoperative atrial fibrillation will allow preventive measures to be used, shorten hospital stays and reduce the risks associated with atrial fibrillation, such as stroke.
Professional highlights
- Member, Biology and Medicine Panel, Research Grants Council, Hong Kong, 2021-2025.
- American Heart Association:
- Member, Review Panel Committee, 2014-2015, 2019, 2021, 2023.
- Chair and co-chair, cardiac electrophysiology and arrhythmia/regulation study group 1994-1996, 2007-2008.
- Fellow, 1987.
- Research director, Division of Heart Rhythm Services, Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 2012-2022.
- National Institutes of Health:
- Ad hoc member, study section, 1993, 1997, 2003, 2004, 2005, 2006, 2021.
- Charter member, electrical signaling, ion transport and arrhythmia study section, 2008-2012.
- Fellow, Heart Rhythm Society, 2008.
- Fellow, American College of Cardiology, 1987.
- Fellow, American College of Physicians, 1985.